Compositions and methods for increasing milk production in animals

ABSTRACT

The invention provides A composition for increasing milk production in an animal that includes an active compound chosen from calcium isopropyl cresol, calcium isopropyl-o-cresol, lactic acid, or combinations thereof, and calcium carbonate as a buffering agent. The invention also provides a composition for increasing milk production in an animal that includes about 0.1 wt % to about 15 wt % of the total weight of the composition of active compound, wherein the active compound is chosen from calcium isopropyl cresol, calcium isopropyl-o-cresol, and lactic acid, about 40 wt % to about 75 wt % of the total weight of the composition of calcium carbonate, and about 10 wt % to about 60 wt % of the total weight of the composition of at least one carrier. The invention also provides a method for increasing milk production in an animal that includes making a composition having an active compound chosen from calcium isopropyl cresol, calcium isopropyl-o-cresol, lactic acid, or combinations thereof, and calcium carbonate as a buffering agent, and feeding the composition to the animal, wherein consumption of the composition increases milk production in the animal.

[0001] This application claims priority of invention under 35 U.S.C.§119(e) from U.S. Provisional Application No. 60/356,846 filed on Feb.13, 2002.

FIELD OF THE INVENTION

[0002] The invention generally relates to compositions and methods ofincreasing the milk production in animals, and more specifically tocompositions that include calcium carbonate and organic phenoliccompounds, and uses thereof.

BACKGROUND OF THE INVENTION

[0003] Modem agricultural practices indicate that the most importantaspect of the milking industry is the feeding of the milking animals. Itis generally thought that correct feeding methods will provide a goodbasis for economic milk production. Correct feeding methods require aproperly balanced feed and a high quality feed. However, even if thesefactors are addressed, issues can arise which may impair the feeding ofthe animals. Some of these issues include coping with heat stress andtimely breed back.

[0004] Often, these issues are addressed through the use of syntheticchemicals or hormones. U.S. Pat. No. 5,565,211 (Rossi) discloses acomposition designed for improving the digestibility of feed forruminants that contains an aromatic phenol derivative, an absorbingsupport, and an aromatizing mixture. U.S. Pat. No. 5,496,571 (Blagdon etal.) discloses a method for increasing the production of milk inruminants that includes oral administration of an increasing amount ofencapsulated choline. U.S. Pat. No. 4,704,276 (Kantor) discloses amethod for increasing lactation in lactating ruminants that includes theadministration of antibiotics. U.S. Pat. No. 4,857,332 (Schricker)discloses a composition for increasing milk fat production in ruminantsthat includes sodium and magnesium antacids, an electrolyte, and sodiumbicarbonate.

[0005] However, there still remains a need for methods of increasingmilk production, especially those that do not utilize syntheticchemicals or hormones.

SUMMARY OF THE INVENTION

[0006] The invention provides compositions that include at least oneactive compound and at least one buffering agent. Active compounds usedin compositions of the invention include an organic phenolic compoundcombined with a Group II salt, and lactic acid. In particular, theorganic phenolic compounds include isopropyl-o-cresol(5-isopropyl-2-methylphenol, or carvacrol) and/or isopropyl-cresol(5-methyl-2[1-methylethyl]phenol, or thymol). The organic phenoliccompound can be obtained from plant oil extracts or synthesized by knownmethods. The Group II salts include a cation from Group II of theperiodic table and an anion, in one embodiment, calcium carbonate. Inanother embodiment, the organic phenolic compound is combined with aGroup II salt to form a reacted compound. Compositions of the inventionalso include buffering agents which function to buffer the stomach orstomachs of the animals.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007]FIG. 1 illustrates the pounds of daily food intake of a dairy herdand the corresponding average daily temperature.

DETAILED DESCRIPTION OF THE INVENTION

[0008] Compositions of the invention are used for increasing milkproduction in animals. The compositions may also increase the appetiteand enhance the general health of the animal. Compositions of theinvention can be administered to any milk producing animals includingthose which are used for production of consumable milk, such as cows,goats, and sheep, and those which produce milk for their young such asmares, and sows. Compositions of the invention may also function topreserve and maintain the quality of feed by reducing or minimizingbacterial growth, such as fungus and yeasts for example, in the feed.

[0009] Because the active compounds of the invention are degraded byenzymes, the compositions are particularly well suited for livestock.Little residue from the active compound is found in products fromtreated livestock, such as milk, eggs, and meat. Organic phenoliccompounds such as isopropyl-o-cresol and isopropyl-cresol are degradedby enzymes into inactive metabolites. The metabolites can be excreted inthe urine (approx. 90%) or expired from the lungs (10%) in the form ofCO₂. Additional information on the degradation of isopropyl-o-cresol andisopropyl-cresol, can be found in US Pharmacopoeia, British and EuropeanPharmacopoeia, and Textbook of Veterinary Physiology, by Prof. Dr. JamesG. Cunningham, Ph.D., 2nd edition. The text of all three references ishereby incorporated by reference herein. Additionally, active compoundsof the invention do not appear to be mutagenic or carcinogenic.

[0010] It is believed, but not relied upon, that the active compounds ofthe invention function as a bactericide. As a bactericide, the activecompounds change the makeup of the flora in the rumen and theintestines. Furthermore, aromatic polyphenolic compounds, which may bepresent when the organic phenolic compounds are extracted from theLamiaceae, or Verbenaceae families, may stimulate receptors for theproduction of enzymes causing an increase in appetite and an enhancedmetabolism.

[0011] Compositions of the invention include at least one activecompound and at least one buffering agent. Compositions of the inventionmay, but need not, include one or more carriers.

[0012] I. Active Compounds

[0013] As used herein, the term “active compound” refers to compoundsformed by reacting an organic phenolic compound with a Group II salt,lactic acid, or combinations thereof.

[0014] A. Organic Phenolic Active Compounds

[0015] 1. Organic Phenolic Compounds

[0016] In one embodiment of the invention, the active compound includesan organic phenolic compound such as isopropyl-o-cresol(5-isopropyl-2-methylphenol, or carvacrol) or isopropyl-cresol(5-methyl-2[1-methylethyl]phenol, or thymol).

[0017] Isopropyl-o-cresol is a crystal with a boiling point of about233° C. at atmospheric pressure. Isopropyl-cresol is a liquid that has aboiling point at atmospheric pressure of 237-238° C. Both compoundsvolatilize in water vapor.

[0018] Organic phenolic compounds, for use in the invention, can be madesynthetically by known methods, or can be obtained from a plant oilextract. In one embodiment, the organic phenolic compounds are obtainedfrom a plant oil extract.

[0019] In an embodiment of the invention wherein the organic phenoliccompounds are obtained from plant oil extracts, the plant is a member ofthe Lamiales order. In another embodiment, the plant is a member of theLamiacea (also called Labiatae) or Verbenaceae families of the orderLamiales, or combinations thereof. Plants in the Lamiaceae andVerbenaceae families include hybrids of plants produced from individualplants in one or a combination of those families.

[0020] The common name for members of the Lamiaceae family, a largefamily of mostly annual or perennial herbs, is the “mint family”. Themint family is classified in the division Magnoliphyta, classMagnoliopsida, and order Lamiales. The Lamiaceae family includes about200 genera, such as Salvia, Rosmarinus, Mentha, Ocimum, Thymus,Marrubium, Monarda, Trichostema, Teucrium, Hyptis, Physostegia, Lamium,Stachys, Scutellaria, Nepeta and Lycopus.

[0021] The common name for members of the Verbenacea family is theVerbena family. The Verbena family is also classified in the divisionMagnoliphyta, class Magnoliopsida, and order Lamiales. The Verbenaceafamily includes about 30 genera, such as Verbena, Lippia, andClerodendrum.

[0022] In one embodiment, plants which are used for extraction oforganic phenolic compounds include, but are not limited to, Ocimum spp.,Saturea spp., Monarda spp, Origanum spp., Thymus spp., Mentha spp.,Nepeta spp., Teucrium gnaphalodes, Teucrium polium, Teucrim divaricatum,Teucrim kotschyanum, Micromeria myrifolia, Calamintha nepela, Rosmarinusofficinalis, Myrtus communis, Acinos suaveolens, Dictamnus albus,Micromeria fruticosa, Cunila origanoides, Mosla Japonoica Maxymowitz,Pycnanthemum nudum, Micromeria Juliana, Piper betel, Trachyspermum ammi,Lippia graveolens, Escholtia splendens, Lippia Graveolens andCedrelopsis grevei, as well as others.

[0023] In one embodiment of a composition of the invention, the oil isextracted from Esholtia splendens, Cedrelopsis grevei, Lippia graveolensor a plant of the species Nepeta, including but not limited to Nepetaracemosa (catmint), Nepeta citriodora, Nepeta elliptica, Nepetahindostoma, Nepeta lanceolata, Nepeta leucophylla, Nepetalongiobracteata, Nepeta mussinii, Nepeta nepetella, Nepeta sibthorpii,Nepeta subsessilis and Nepeta tuberosa.

[0024] In another embodiment of a composition of the invention, the oilis extracted from a hybrid plant produced from Nepeta racemosa, Esholtiasplendens, Cedrelopsis grevei, and Lippia graveolens. The hybrid plantcan be produced by known methods, but in one embodiment is produced bysimple known crossing over techniques.

[0025] 2. Extraction of Organic Phenolic Compounds from Plants

[0026] a. Cultivating the Plant

[0027] Plants of the Lamiaceae and Verbenacea families are foundthroughout the world and are relatively easy to cultivate. To cultivatethe plants, seeds, in one embodiment, those of plants that are expectedto yield a high percentage (e.g., at least about 70 wt %, morepreferably at least about 80 wt %), of organic phenolic compounds, areplanted in fine loose soil, preferably in a sub-tropical climate. Hybridseeds having a high percentage of organic phenolic compounds can beproduced by known techniques. Crossing Nepeta racemosa, Esholtiasplendens, Cedrelopsis grevei, and Lippia graveolens produces one suchhybrid that is a source of the organic phenolic compounds in oneembodiment of the invention. The seeds are then cultivated using knownagricultural techniques, such as watering, and artificial fertilizing.In one embodiment, the plants are cultivated and grown without the useof any synthetic pesticides.

[0028] Because the leaves contain a high amount of oil upon blossoming,it is preferred that the plants be harvested soon after the plants beginto blossom. In one embodiment, the plants are harvested within 24 hoursafter blossoming, in another embodiment, within 12 hours afterblossoming. In yet another embodiment, harvesting is undertaken early inthe morning or late in the evening hours (after blossoming begins) whenthe leaves are not exposed to the sun.

[0029] Because the majority of the oil is found in the leaves andblossoms of the plant, in one embodiment of the invention only theleaves and blossoms are utilized in the extraction process. Use of otherparts of the plant may increase impurities and decrease yield, but maybe utilized in some embodiments of the invention.

[0030] b. Extracting Oil from the Plant

[0031] Oil containing organic phenolic compounds can be extracted fromeither dried or fresh plants, or a combination of both. If the plant isdried, in one embodiment, the drying process is undertaken in specialdrying houses that are constructed to allow for constant, freecirculation of air. In another embodiment, the harvested leaves andblossoms are not exposed to direct sunlight, as exposure to sunlight mayreduce the amount of active material present in the leaves.

[0032] To dry the product, the leaves and blossoms are arranged in 20-25cm thick layers. To promote uniform drying, the layers should be turnedup-side-down either manually or mechanically four times a day during thefirst three days of drying. Generally, the leaves are dried for about 7to 8 days. After the leaves and blossoms are dried, the oil can beextracted by known methods, including distillation methods such as steamdistillation.

[0033] In one embodiment of the invention, the oil is extracted in a twostage distillation process (double distillation). In another embodiment,the oil is first extracted by steam distillation (at a temperature ofabout 100° C.) to remove most impurities. Typically, after the firststeam distillation, the extracted oil contains about 3% to about 4% byweight thymol; about 60% to about 70% carvacrol and about 26% to about37% by weight impurities.

[0034] The steam-distilled oil is then distilled again at a temperaturebetween about 180° C. to about 200° C. to remove additional impurities.In yet another embodiment, the redistilled oil is distilled yet again (adouble re-distillation). If a double re-distillation process is used,the oil typically has a purity of greater than 90%, more preferablygreater than 95%, and most preferably to 99%. Although yield tends to belower when a double re-distillation process is used, typically about 1to 10 kilograms, more typically about 3 to 7 kilograms of oil, areobtained for every 100 kilograms of dried leaves and blossoms.

[0035] In a steam distillation process, the distillation columngenerally has two output tubes: one for oil (at the base of the column)and one for water vapor (at the top of the column). A water source ispositioned under the leaves and blossoms and is heated to about 100° C.preferably under a pressure of about 20 bar to about 25 bar (increasedpressure will tend to reduce the distillation time). The steam passesthrough the leaves and blossoms, thereby creating oil droplets. Becausethe water vapor is lighter than the oil droplets, the water dropletsflow out of the output tube positioned at the top of the distillationcolumn and the oil droplets flow out of the output tube positioned atthe base of the distillation column. The distillation process is carriedout for about 1 to about 5 hours, more typically about 2 to about 3hours.

[0036] In one embodiment of the invention, distillation of plant oilsresults in separation of isopropyl cresol and isopropyl-o-cresol fromaromatic polyphenolic compounds. In one embodiment of the invention,these aromatic polyphenolic compound are added to a composition of theinvention. Examples of such aromatic polyphenolic compounds include butare not limited to pimen, cimen, linalool, and barneol. Alternatively,these aromatic polyphenolic compounds may be separately obtained byeither extraction or synthesis, and added to a composition of theinvention. It is thought, but not relied upon, that the aromaticpolyphenolic compounds may improve the appetite of an animal they arefed to.

[0037] 3. Synthetic Production of Organic Phenolic Compounds

[0038] Organic phenolic compounds used in the invention canalternatively be prepared by synthetic methods. Methods forsynthetically producing organic phenolic compounds such as carvacrol andthymol are known. See for example Organic Chemistry by Morrison & Boyd,2d ed. 1971 at page 815. Additionally, these compounds are availablefrom chemical manufacturers and are listed in the Merck Index. Althoughthe organic phenolic compounds may be synthetically produced asmentioned above, in one embodiment the compounds are extracted fromplants. Because phenol is used to synthesize isopropyl-o-cresol andisopropyl-cresol, the resulting product tends to contain residual phenol(less than 1%). It is generally undesirable to administer a compositioncontaining phenol to an animal because phenol can be mutagenic andcarcinogenic.

[0039] 4. Group II Salt

[0040] The organic phenolic compound is combined with a salt, in oneembodiment of the invention, a Group II salt. A Group II salt refers toan ionic molecule that has as its cation one of the elements in Group IIof the periodic chart of elements (Beryllium (Be), Magnesium (Mg),Calcium (Ca), Strontium (Sr), Barium (Ba), or Ruthenium (Ru)). Group IIsalts as used herein include any Group II cation in combination with anyanion. Examples of Group II salts include for example Group IIchlorides, Group II hydroxides, and Group II carbonates. In oneembodiment Group II salts include Group II carbonates, in anotherembodiment the Group II salt is calcium carbonate.

[0041] In one embodiment, the Group II salt is combined with the organicphenolic compound to form a reacted organic phenolic compound thatincludes two deprotonated organic phenolic compounds associated with theGroup II cation.

[0042] Specific exemplary methods of forming these compounds of theinvention are provided below. The Group II salts can be combined withthe organic phenolic compounds in a molar ratio of about two (2) molesorganic phenolic compound to one (1) mole Group II salt. In oneembodiment, the Group II salt is calcium carbonate, in this instance,the calcium carbonate is combined with the organic phenolic compound inratios (by weight of the total composition) in the range of about 50 wt% to about 90 wt % organic phenolic compound to about 10 wt % to about50 wt % Group II salt. In another embodiment, the ratio of organicphenolic compound to Group II salt is within the range of about 60 wt %to about 90 wt % organic phenolic compound to about 10 wt % to about 40wt % Group II salt. In yet another embodiment, the ratio of organicphenolic compound to Group II salt is about 70 wt % to about 80 wt %organic phenolic compound to about 20 wt % to about 30 wt % Group IIsalt. In even yet another embodiment, about 75 wt % organic phenoliccompound is combined with about 25 wt % Group II salt.

[0043] 5. Reaction to form Organic Phenolic Active Compound

[0044] An “active compound” may refer to a compound formed by chemicallyreacting isopropyl-o-cresol or isopropyl-cresol with a Group II salt,such as calcium carbonate. The active compound products of the reactionof isopropyl cresol, and isopropyl-o-cresol with calcium carbonate areshown below.

[0045] As used herein, the term “reacting” refers to a process in whichthe organic phenolic compound is chemically modified (as compared to theformation of a solution). In the formation of an active compound with aGroup II salt, the reaction of the organic phenolic compound involvesdeprotonation of the alcohol moieties on two organic phenolic compoundsto form aryl oxide anions which then associate with the Group II cationin solution.

[0046] The reaction can be made to take place by known methods,including but not limited to stirring, heating, refluxing, ormodification of the pressure. In one embodiment, the reaction isundertaken in a high speed mixer under pressure. In one embodiment, thepressure in the mixer can range from about 2 atm to about 4 atm,specifically about 3 atm (70 kilopounds/m²).

[0047] In one embodiment, the solid reacted active compound may bepurified, for example, by recrystallization. In purification byrecrystallization, a solvent is selected in which the compound issoluble at higher temperatures, but only slightly soluble at lowertemperatures, so that the compound will pass from solution toprecipitate at a lower temperature while impurities remain in solution.

[0048] For example, the active compound can be combined with ethanol toproduce a suspension. The suspension is then heated until it boils.Ethanol is added dropwise to the heated suspension until the reactedactive compound is completely dissolved. The mixture is then cooled toprecipitate the purified active compound. Generally, pure activecompound will precipitate at a lower temperature than impurities.

[0049] The active compound can also be purified by certainchromatographic methods, including but not limited to solid-liquid,liquid-liquid, and gas-liquid type chromatography. Examples ofsolid-liquid type chromatographic methods that could be utilized includecolumn chromatography, gel chromatography, dry-column chromatography, orhigh performance liquid chromatography (HPLC).

[0050] In one embodiment of the invention, two or more organic phenolicactive compounds are combined. For example, one or more differentorganic phenolic compounds that have been reacted with a Group II saltcan be combined with one or more different organic phenolic compoundsthat have been reacted with a Group II salt. In another embodiment, oneor more organic phenolic compounds that have been reacted with a GroupII salt can be combined with one or more organic phenolic compounds thathave been reacted with a different Group II salt. For example, an activecompound obtained by reacting calcium carbonate with isopropyl-o-cresolcan be mixed with an active compound obtained by reacting calciumcarbonate with isopropyl cresol.

[0051] In one embodiment, reacted isopropyl-o-cresol and reactedisopropyl-cresol are combined to form a mixture. In another embodiment,the mixture contains more isopropyl-o-cresol active compound thanisopropyl-cresol active compound. For example, the mixture can containbetween about 1 wt % to about 45 wt % of the weight of the total mixtureof the active compound isopropyl cresol active compound and betweenabout 55 wt % and about 99 wt % of the weight of the total mixture ofthe active compound isopropyl-o-cresol active compound; in anotherembodiment between about 1 wt % to about 25 wt % of the weight of thetotal mixture of the active compound isopropyl cresol active compoundand between about 75 wt % and about 99 wt % of the weight of the totalmixture of the active compound isopropyl-o-cresol active compound; inyet another embodiment between about 1 wt % to about 10 wt % of theweight of the total mixture of the active compound isopropyl cresolactive compound and between about 90 wt % and about 99 wt % of theweight of the total mixture of the active compound isopropyl-o-cresolactive compound; in even yet another embodiment between about 1 wt % toabout 5 wt % of the weight of the total mixture of the active compoundisopropyl cresol active compound and between about 95 wt % and about 99wt % of the weight of the total mixture of the active compoundisopropyl-o-cresol active compound. In a further embodiment, a mixtureis obtained by mixing 5 wt % isopropyl cresol active compound with 95 wt% isopropyl-o-cresol active compound. Again, mixing can be carried outby any method known to those of skill in the art, including but notlimited to mixing at 150 revolutions per minute for at least 5 minutesto produce a homogenous mixture.

[0052] B. Lactic Acid

[0053] The term active compound can also include lactic acid, C₃H₆O₃,the structure of which can be seen below.

[0054] Lactic acid is a solid with a melting point of 16.8° C. Lacticacid can be prepared technically by “lactic acid fermentation” ofcarbohydrates such as glucose, sucrose, and lactose with Bacillus acidilacti or related organisms such as Lactobacillus delbrueckii, and L.bulgaricus. This fermentation is generally carried out at relativelyhigh temperatures. Lactic acid can also be produced commercially byfermentation of whey, cornstarch, potatoes, or molasses.

[0055] Lactic acid is thought to function in compositions of theinvention as a bactericide. It can be used in combinations with the basereacted active compounds of the invention.

[0056] In embodiments of the invention including lactic acid in theactive compound, the lactic acid is about 10 wt % to about 90 wt % ofthe weight of the active compound. In yet another embodiment, the lacticacid is about 30 wt % to about 70 wt % of the weight of the activecompound. In even yet another embodiment, the lactic acid is about 40 wt% to about 60 wt % of the weight of the active compound. A furtherembodiment has about 50 wt % of the weight of the active compound oflactic acid.

[0057] II. Compositions

[0058] As used herein, the term “composition” refers to a compositionwhich includes at least one active compound and a buffering agent.Alternatively, a “composition” can contain other components includingbut not limited to one or more carriers. For example, the term“composition” can refer to a combination of one or more reacted organicphenolic compounds, one or more buffering agents, and one or morecarriers. This definition of “composition” includes essential oilsobtained from plants as well as synthetically produced organic phenoliccompounds combined with acceptable buffering agents, and carriers.

[0059] A. Active Compounds

[0060] In one embodiment of the invention, a composition of theinvention includes one or more active compounds (e.g., calciumisopropyl-o-cresol, calcium isopropyl-o-cresol, or lactic acid), orcombinations thereof. In one embodiment, the total amount of activecompound makes up about 0.1 wt % to about 15 wt % of the total weight ofthe composition. In another embodiment the total amount of activecompound makes up about 0.5 wt % to about 12 wt % of the total weight ofthe composition. In an embodiment of the invention which has onlyorganic phenolic active compounds, the total amount of active compoundsmakes up about 4 wt % to about 6 wt % of the total weight of thecomposition, and in another embodiment about 5 wt % of the total weightof the composition.

[0061] In an embodiment of the invention which has organic phenolicactive compounds and lactic acid compounds, the total amount of activecompounds makes up about 8 wt % to about 12 wt % of the total weight ofthe composition, and in another embodiment about 10 wt % of the totalweight of the composition.

[0062] B. Buffering Agents

[0063] In one embodiment of the invention a buffering agent can enhancethe digestive functioning of the animal and can aid in counteracting theeffects of heat stress. Compositions of the invention may also includeat least one buffering agent. Buffering agents function to buffer thestomachs of the animals that consume the buffering agent. In cows, abuffering agent functions to aid in digestion of fiber in the cow'sdiet. A dairy cow has a complex acid-base regulatory system with the pHof the rumen generally varying from about 5.5 to 6.8. If the pH of therumen is not optimal, microbial yield and efficiency drops, dry matterintake declines, and metabolic disorders can increase. In oneembodiment, a rumen buffering agent ties up hydrogen ions near thedesired rumen pH.

[0064] In one embodiment of the invention, the buffering agent used iscalcium carbonate (CaCO₃). Calcium carbonate can be obtained fromlimestone sources. Limestone can be deposited by cold water or hotwater. The cold water deposited calcium carbonate is a grayish materialthat is very hard and dense. Generally, cold water deposited calciumcarbonate has a slow reaction time. Hot water deposited calciumcarbonate is a white, soft material with a fast reaction time.

[0065] Reaction time of a buffering agent can be determined by a numberof known methods. One example of such a method follows. Five hundred(500) mL of distilled H₂O is measured into a beaker equipped with astirrer (alternatively, a blender can also be used). A precisely weighed1.00 gram sample of the buffering agent is added, and the solution isstirred. At the same time, a pH meter is inserted into the solution. 2.3mL of glacial acetic acid is quickly injected, and a timer is started.The pH of the solution is monitored until it reaches 4.1. The time ittakes the solution to reach this pH is one measurement of the reactiontime.

[0066] It is thought, but not relied upon, that a reaction time of 120to 140 seconds allows a buffering agent (calcium carbonate for example)to buffer all of the stomachs of a cow. Buffering of the stomachs isimportant for full utilization of the feed before it passes through thecow. In one embodiment of the invention, the calcium carbonate utilizedas the buffering agent has a reaction time of about 120 to about 140seconds. In another embodiment, the calcium carbonate used has areaction time of about 130 to about 140 seconds. In yet anotherembodiment, the calcium carbonate has a reaction time of about 135 toabout 140 seconds, specifically, about 136 seconds.

[0067] In one embodiment, compositions of the invention include about 40wt % to about 75 wt % buffering agent based on the total weight of thecomposition. In another embodiment, compositions of the inventioninclude about 50 wt % to about 65 wt % of the total weight of thecomposition. In yet another embodiment that includes both organicphenolic compounds and lactic acid as active compounds, the bufferingagent is about 55 wt % of the total weight of the composition. In anembodiment of the invention having only organic phenolic compounds asthe active compounds, the buffering agent is about 60 wt % of the totalweight of the composition.

[0068] C. Carriers

[0069] Compositions of the invention may, but need not include acarrier. Carriers used in compositions of the invention can function togive desired characteristics to the compositions of the invention.Examples of such desired characteristics include but are not limited toflowability of the composition, texture of the composition, or stabilityof the composition.

[0070] Any materials that can impart these desired characteristics, andare not detrimental to the animal may be utilized if desired, ascarriers in compositions of the invention. In one embodiment of theinvention materials that can be used as carriers include but are notlimited to cornstarch and silicon dioxide.

[0071] In one embodiment of a composition of the invention, the carrieris about 10 wt % to about 60 wt % of the total weight of thecomposition. In yet another embodiment, the carrier is about 25 wt % toabout 45 wt % of the total weight of the composition. In yet anotherembodiment, the carrier is about 30 wt % to about 40 wt % of the weightof the total composition. In a further embodiment, the carrier is about35 wt % of the total weight of the composition.

[0072] In one embodiment of a composition of the invention, the carrierincludes both corn starch and silicon dioxide. In this embodiment, thesilicon dioxide is about 5 wt % to about 20 wt % of the weight of thecarrier and the corn starch is about 80 wt % to about 95 wt % of theweight of the carrier. In another embodiment, the silicon dioxide isabout 7.5 wt % to about 17.5 wt % of the weight of the carrier and thecorn starch is about 82.5 wt % to about 92.5 wt % of the weight of thecarrier. In yet another embodiment, the silicon dioxide is about 10 wt %to about 15 wt % of the total weight of the carrier, and the corn starchis about 85 wt % to about 90 wt % of the carrier. In a furtherembodiment, the silicon dioxide is about 14 wt %, and the corn starch isabout 86 wt % of the carrier ( also illustrated as the silicon dioxidebeing about 5 wt % of the total weight of the composition and the cornstarch being about 30 wt % of the total weight of the composition).

[0073] D. Illustrative Compositions

[0074] An illustrative formulation of a composition of the invention foradministration to cows, sheep, and goats is illustrated below.Ingredient Weight Percent Calcium Isopropyl cresol 0.25 CalciumIsopropyl-o-cresol 4.75 Calcium Carbonate 60.0 Silicon Dioxide 5.0 CornStarch 30.0 100.

[0075] An illustrative formulation of a composition of the invention foradministration to mares and sows is illustrated below. Ingredient WeightPercent Calcium Isopropyl cresol 0.25 Calcium Isopropyl-o-cresol 4.75Lactic Acid 5.0 Calcium Carbonate 55.0 Silicon Dioxide 5.0 Corn Starch30.0 100.

[0076] E. Dosage and Administration

[0077] In one embodiment of the invention, compositions of the inventionare mixed with feed. Dosage amounts for compositions of the inventionrange from about 500 parts per million (ppm) to about 2500 ppm. In oneembodiment, dosage amounts for compositions of the invention range fromabout 750 ppm to about 1500 ppm. In another embodiment, dosage amountsfor compositions of the invention range from about 900 ppm to about 1100ppm, and yet another embodiment has a dosage amount of about 1000 ppm.

[0078] In an embodiment where the composition is being administered toanimals that are being used for milk production, a composition of theinvention is administered to the animals permanently. In embodimentswhere animals are feeding their own young the milk, a composition of theinvention is administered to the animals only during the suckling periodof the young animals. For example, in one embodiment of the inventionused for milk production in mares, a composition of the invention isadministered from (age of young animal) day 1 until day 180 (forapproximately 6 months). In another embodiment of the invention used forincreasing milk production in sows, a composition of the invention isadministered two weeks before delivery of the piglets and for 14 daysthereafter.

WORKING EXAMPLES Example 1

[0079] Extraction of Isopropyl-1-cresol and Isopropyl Cresol from Nepetacataria

[0080] Isopropyl-o-cresol and isopropyl-cresol were extracted fromNepeta cataria using a two stage distillation process. In the firststage, dried leaves were extracted using a steam distillation process.After the distillation, the oil is cooled to room temperature for atleast 72 hours.

[0081] The oil from the steam distillation process was then re-distilledin a second stage distillation process. In the re-distillation, the oilwas heated to a temperature of about 186° C. for about 1 hour to removeremaining impurities such as linalool, barneol, pimen, cimen etc.Generally, the impurities have a boiling point of about 150° C. Incontrast, both isopropyl-o-cresol and isopropyl-cresol have a boilingpoint of about 230° C. to 240° C. Thus, a temperature of 180° C. willtypically not remove or damage the organic phenolic products.

[0082] The oil is again allowed to cool for at least 72 hours tostabilize the oil.

[0083] After the oil is cooled, the redistillation is repeated at atemperature of 180° C. for 30 minutes to eliminate almost all of theremaining impurities. The double re-distillation process produced an oilhaving a purity between 95% and 98%.

[0084] After the second re-distillation the oil was allowed to cool forat least 72 hours before production.

Example 2

[0085] Separation of Isopropyl-o-cresol from Isopropyl-cresol

[0086] Isopropyl-o-cresol and isopropyl-cresol were separated byincubating the distilled oil at a temperature of −25° C. for 6 hours.Isopropyl-o-cresol remains as a liquid and isopropyl-cresol isprecipitated out as crystals. The two compounds were then separated viafiltration.

Example 3

[0087] Preparation of a Composition of the Invention for Cows, Sheep, orGoats

[0088] Isopropyl cresol and isopropyl-o-cresol were produced using themethod of examples 1 and 2 above. Polyphenolic compounds were alsoproduced during the distillation and separated out. The isopropyl cresolwas then combined in a 2:1 molar ratio with calcium carbonate from a hotwater deposited limestone. This mixture was combined in an atomizerunder vacuum-pressure to create the calcium isopropyl cresol activecompound. The isopropyl-o-cresol was then combined in a 2:1 molar ratiowith calcium carbonate from a hot water deposited limestone. Thismixture was combined in an atomizer under vacuum-pressure to create thecalcium isopropyl-o-cresol active compound. Calcium isopropyl cresol wascombined with calcium isopropyl-o-cresol in a 95:5 weight ratio andmixed.

[0089] A composition was then formed from 5 wt % of the calciumisopropyl cresol/calcium isopropyl-o-cresol mixture, 60 wt % calciumcarbonate from a hot water deposited limestone, 5 wt % silicon dioxide,and 30 wt % corn starch. To this composition was readded thepolyphenolic compounds from the distillation of the plant essentialoils.

Example 4

[0090] Preparation of a Composition of the Invention for Mares and Sows

[0091] Isopropyl cresol and isopropyl-o-cresol were produced using themethod of examples 1 and 2 above. Polyphenolic compounds were alsoproduced during the distillation and separated out. The isopropyl cresolwas then combined in a 2:1 molar ratio with calcium carbonate from a hotwater deposited limestone. This mixture was combined in an atomizerunder vacuum-pressure to create the calcium isopropyl cresol activecompound. The isopropyl-o-cresol was then combined in a 2:1 molar ratiowith calcium carbonate from a hot water deposited limestone. Thismixture was combined in an atomizer under vacuum-pressure to create thecalcium isopropyl-o-cresol active compound. Calcium isopropyl cresol wascombined with calcium isopropyl-o-cresol in a 95:5 weight ratio andmixed.

[0092] 5 wt % of the calcium isopropyl cresol/calcium isopropyl-o-cresolmixture was then added to 5 wt % lactic acid, followed by 55 wt %calcium carbonate from a hot water deposited limestone, 5 wt % silicondioxide, and 30 wt % corn starch.

Example 5

[0093] Use of a Composition of the Invention on Cows

[0094] One hundred (100) milk cows that would normally have a decreasedfeed intake and milk production due to heat stress were administered acomposition of the invention according to Example 3 beginning in thefirst part of June.

[0095] Within four weeks of beginning treatment, the Total Mix Ration(feed amount) was increased by 1300 pounds (590 kg).

Example 6

[0096] Use of a Composition of the Invention on Cows

[0097] A herd of 116 cows were administered a composition of theinvention according to Example 3. This herd was compared with a 127 cowherd without administration of a compound of the invention. Thecomparison was carried out in June.

[0098] The herd being administered the composition of the invention hadan increased intake of food and an increased level of milk productioncompared to a decreased intake of food and a decreased level of milkproduction in the herd without administration of the composition.

Example 7

[0099] Use of a Composition of the Invention on Cows

[0100] Twenty (20) cows in a 100 cow herd had a previously uncuredSalmonella outbreak. The cows were fed a composition of the inventionaccording to Example 3.

[0101] Within 2 days of beginning treatment, the diarrhea caused by theSalmonella was gone, and the cows were back to their pre-outbreak levelof milk production in 7 to 10 days.

Example 8

[0102] Use of a Composition of the Invention on Cows

[0103] A composition of the invention according to Example 3 wasadministered to 67 cows and it doubled the rate of milk production andhad positive effects on winter dysentery.

Example 9

[0104] Use of a Composition of the Invention on Cows

[0105] A composition of the invention according to Example 3 wasadministered to 120 cows. The milk production of the cows increased 4pounds (8.8 kg) per cow per day and the herd was in an overall bettercondition.

Example 10

[0106] Use of a Composition of the Invention on Cows

[0107] A dairy herd with 90 cows was given a composition of theinvention according to Example 3. Another dairy herd (owned by the sameindividual) with 50 cows was not given a composition of the invention.

[0108] The herd being administered the composition of the invention hadan increased milk production of 2 to 3 pounds (4.4 to 6.6 kg) per cowper day, stronger heats, and had no winter dysentery problems. The herdwithout the composition of the invention had a milk production that wasdecreased from normal, weaker heats, and the entire herd was afflictedwith winter dysentery.

Example 11

[0109] Use of a Composition of the Invention on Cows

[0110] A herd of 2500 cows was treated for 30 days with a composition ofthe invention according to Example 3. The consumption of feed increasedan average of 1.5 pounds (3.3 kg) per cow per day. The milk productionincreased an average of 3 pounds (6.6 kg) per cow per day within 12 daysof administering the composition.

[0111] After 30 days, the administration of the composition of theinvention was ceased, and within 48 hours, there was an average of a 3pound (6.6 kg) drop in milk production.

Example 12

[0112] Use of a Composition of the Invention on Cows

[0113] A 123 cow herd was treated for 7 days with a composition of theinvention according to Example 3. The 10 days prior to the treatment,there was an average of 51.12 pounds (113 kg) of milk having 3.91%butter fat, 3.01% protein, and a Somatic cell count of 231. The seventhday after beginning treatment with the composition of the invention,there was 52.24 pounds (115 kg) of milk with 4.04% butter fat, 3.13%protein, and a Somatic cell count of 21 1.

Example 13

[0114] Use of a Composition of the Invention on Cows

[0115] A herd of 70 cows were administered a composition of theinvention according to Example 3 for three weeks (November 29-December18).

[0116] There was an average increase of milk production of 4.3 pounds(9.5 kg) per cow per day. The solids in the milk increased, and thebutter fat and the protein were stable.

Example 14

[0117] Use of a Composition of the Invention on Cows

[0118] An 80 cow herd was administered a composition of the inventionaccording to Example 3 for two weeks.

[0119] The cows had an average of a 1 to 1½ pound (2.2 to 3.3 kg) percow per day increase in milk production. The milk had an increasedbutter fat and protein amount and had a decreased Somatic cell count.The cattle also seemed to be walking better, and had a better appetite.

Example 15

[0120] Use of a Composition of the Invention on Cows

[0121] A 100 cow dairy herd was monitored for 60 days (Jun. 1, 2001 toJul. 27, 2001) while being administered a composition of the inventionaccording to Example 3. The average daily temperature was also noted forthose days.

[0122]FIG. 1 shows a graph of the average daily temperature in degreesFahrenheit and the amount of feed consumed by the animals over the 60day period.

Example 16

[0123] Effect of A Composition of the Invention on Feed

[0124] A composition of the invention according to Example 3 above wasadded at the rate of 0.16 grams per 0.55 kg (0.25 lbs) of feed. Thisamount would correlate to 0.22 kg (0.10 lbs) of the composition per cowper day.

[0125] The treated feed was monitored for molds, and the molds wereidentified and counted. The following results were obtained with awithout addition of a composition of the invention. TABLE 1 Amount ofspecified Amount of specified mold in 0.55 kg of feed mold in 0.55 kgfeed without a composition with a composition Type of Mold of theinvention of the invention Mucor sp. 10,000 100 Penicillum sp. 200 0Yeast Count 17,989,800 8,999,900 Total Count 18,000,000 9,000,000

[0126] These results show that compositions of the invention may alsohave antioxidant properties. These properties help maintain thecondition or “freshness” of the feed keeping it palatable to the animalfor a longer period of time.

[0127] The above specification, examples and data provide a completedescription of the manufacture and use of the composition of theinvention. Since many embodiments of the invention can be made withoutdeparting from the spirit and scope of the invention, the inventionresides in the claims hereinafter appended.

What is claimed is:
 1. A composition for increasing milk production inan animal comprising: (a) an active compound chosen from the groupconsisting of calcium isopropyl cresol, calcium isopropyl-o-cresol,lactic acid, or combinations thereof; and (b) calcium carbonate as abuffering agent.
 2. The composition of claim 1, wherein said activecompound consists of calcium isopropyl cresol and calciumisopropyl-o-cresol.
 3. The composition of claim 2, wherein said calciumisopropyl cresol and calcium isopropyl-o-cresol are present in a weightratio of about 1:99 to about 45:55.
 4. The composition of claim 3,wherein said calcium isopropyl cresol and calcium isopropyl-o-cresol arepresent in a weight ratio of about 1:99 to about 10:90.
 5. Thecomposition of claim 4, wherein said calcium isopropyl cresol andcalcium isopropyl-o-cresol are present in a weight ratio of about 5:95.6. The composition of claim 1, wherein said active compound is about 0.1wt % to about 15 wt % of the total weight of said composition.
 7. Thecomposition of claim 6, wherein said active compound is about 0.5 wt %to about 12 wt % of the total weight of said composition.
 8. Thecomposition of claim 7, wherein said active compound is about 4 wt % toabout 6 wt % of the total weight of said composition.
 9. The compositionof claim 8, wherein said active compound is about 5 wt % of the totalweight of said composition.
 10. The composition of claim 1, wherein saidactive compound is obtained from reaction of an organic phenoliccompound with a calcium salt.
 11. The composition of claim 10, whereinsaid organic phenolic compound is obtained from a plant extract.
 12. Thecomposition of claim 11, wherein said plant is from the order Lamiales.13. The composition of claim 12, wherein said plant is from the familyLamiaceae, Verbenaceae, or combinations thereof.
 14. The composition ofclaim 13, wherein the plant is a hybrid of Nepeta racemosa, Esholtiasplendens, Cedrelopsis grevei, and Lippia graveolens.
 15. Thecomposition of claim 1, wherein said active compound is a mixture ofcalcium isopropyl cresol, calcium isopropyl-o-cresol, and lactic acid.16. The composition of claim 15, wherein said active compound is about0.1 wt % to about 15 wt % of the total weight of said composition. 17.The composition of claim 16, wherein said active compound is about 0.5wt % to about 12 wt % of the total weight of said composition.
 18. Thecomposition of claim 17, wherein said active compound is about 8 wt % toabout 12 wt % of the total weight of said composition.
 19. Thecomposition of claim 18, wherein said active compound is about 10 wt %of the total weight of said composition.
 20. The composition of claim 1,wherein said calcium carbonate is hot water deposited.
 21. Thecomposition of claim 1, wherein said calcium carbonate has a reactiontime of about 120 to about 160 seconds.
 22. The composition of claim 21,wherein said calcium carbonate has a reaction time of about 120 to about140 seconds.
 23. The composition of claim 1, wherein said bufferingagent is about 40 wt % to about 75 wt % of the total weight of saidcomposition.
 24. The composition of claim 23, wherein said bufferingagent is about 50 wt % to about 65 wt % of the total weight of saidcomposition.
 25. The composition of claim 1, further comprising acarrier.
 26. The composition of claim 25, wherein said carrier is chosenfrom the group consisting of silicon dioxide, and corn starch.
 27. Thecomposition of claim 1, wherein said animal is chosen from the groupconsisting of cows, sheep, and goats.
 28. The composition of claim 1,wherein said animal is chosen from the group consisting of mares andsows.
 29. The composition of claim 1, wherein said composition is mixedwith food for said animal.
 30. The composition of claim 29, wherein saidcomposition is mixed with food at a concentration of from about 500 ppmto about 2500 ppm.
 31. The composition of claim 30, wherein saidcomposition is mixed with food at a concentration of about 1000 ppm. 32.The composition of claim 1, further comprising at least one aromaticpolyphenolic compounds.
 33. The composition of claim 32, wherein saidaromatic polyphenolic compounds are obtained from a plant extract. 34.The composition of claim 33, wherein said plant extract also provides anorganic phenolic compound.
 35. The composition of claim 32, wherein saidaromatic polyphenolic compound is chosen from the group consisting ofpimen, cimen, linalool, bameol, and combinations thereof.
 36. Acomposition for increasing milk production in an animal comprising: (a)about 0.05 wt % to about 0.5 wt % of the total weight of saidcomposition of calcium isopropyl cresol; (b) about 4.5 wt % to about4.95 wt % of the total weight of said composition of calciumisopropyl-o-cresol; (c) about 1.75 wt % to about 7 wt % of the totalweight of said composition of silicon dioxide; (d) about 28 wt % toabout 33.25 wt % of the total weight of said composition of corn starch;and (e) about 55 wt % to about 60 wt % of the total weight of saidcomposition of calcium carbonate.
 37. The composition of claim 36,further comprising at least one aromatic polyphenolic compound.
 38. Acomposition for increasing milk production in an animal comprising: (a)about 0.05 wt % to about 0.5 wt % of the total weight of saidcomposition of calcium isopropyl cresol; (b) about 4.5 wt % to about4.95 wt % of the total weight of said composition of calciumisopropyl-o-cresol; (c) about 3 wt % to about 7 wt % of the total weightof said composition of lactic acid (c) about 1.75 wt % to about 7 wt %of the total weight of said composition of silicon dioxide; (d) about 28wt % to about 33.25 wt % of the total weight of said composition of cornstarch; and (e) about 50 wt % to about 55 wt % of the total weight ofsaid composition of calcium carbonate.
 39. The composition of claim 38,further comprising at least one aromatic polyphenolic compound.
 40. Amethod for increasing milk production in an animal comprising the stepsof: (a) making a composition, according to claim 1; and (b) feeding saidcomposition to the animal, wherein consumption of the compositionincreases milk production in the animal.
 41. The method of claim 40,further comprising mixing said composition with feed before feeding itto said animal.
 42. The method of claim 41, wherein said composition isadded to said feed at a concentration of about 500 to about 2500 ppm.43. The method of claim 42, wherein said composition is added to saidfeed at a concentration of about 1000 ppm.
 44. The method of claim 40,wherein said composition is feed to the animal continuously.
 45. Themethod of claim 40, wherein said composition is feed to the animal atleast before and after giving birth.
 46. The method of claim 45, whereinsaid composition is feed to the animal for 14 days before giving birthand for 14 days after giving birth.
 47. A method of reducing orminimizing bacterial growth in animal feed comprising the steps of: (a)making a composition according to claim 1,; and (b) mixing saidcomposition with animal feed, wherein said composition minimizes orreduces the bacterial growth in said animal feed.
 48. The method ofclaim 47, wherein said bacterial growth comprises growth of yeast,fungus, or combinations thereof.
 49. The method of claim 47, whereinsaid composition is added to said animal feed at a concentration ofabout 500 to about 2500 ppm.
 50. The method of claim 49, wherein saidcomposition is added to said animal feed at a concentration of about1000 ppm.